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*Only for medical professionals to read and refer to the new PFS of Anlotinib and Osimertinib for up to 9 months! Osimertinib is the third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI).
Osimertinib has been recommended by major authoritative guidelines and has become the standard treatment for second-line EGFR T790M mutation-positive NSCLC patients means.
At present, there is no standard for the treatment of non-small cell lung cancer (NSCLC) patients after osimertinib resistance in China.
Which treatment plan can bring greater survival benefits to patients? This article will use a real case to discuss the follow-up treatment of osimertinib resistance.
Case 1 The patient is female, 52 years old.
In June 2017, due to coughing for more than one month, I came to the hospital for treatment.
Chest CT showed that the right lower lung was consolidated, accompanied by right pleural effusion and miliary disseminated lung opacity.
PS score: 1.
Fiberoptic bronchoscopy + pathological examination revealed: stage IV (cTxNxM1) lung adenocarcinoma.
Genetic test: ARMS-PCR test found EGFR 19del.
1 T790M mutation appeared after gefitinib resistance.
In June 2017, because the patient's genetic test was EGFR 19del, gefitinib was selected as the first-line treatment for the patient.
In September 2017, imaging examination showed that the lesion reached partial remission (PR).
In January 2018, the image showed the disease progression, and the progression-free survival (PFS) was 7 months.
After the disease progressed in the first-line treatment of gefitinib, blood samples of the patient were tested and found a common mutation of EGFR 19 del (pE746_A750del, allele frequency (AF): 0.
07%) and T790M (AF: 0.
16%). In February 2018, the patient was switched to osimertinib for second-line treatment, and the efficacy evaluation reached PR.
In December 2018, chest CT scan showed enlarged right lung lesions, increased pleural effusion, and disease progression.
PFS was 10 Months.
2nd generation + 3rd generation EGFR-TKI: After osimertinib drug resistance, the second-line osimertinib treatment failed, NGS test was performed, and EGFR 19del, T790M, and T790M-C797S trans mutations were found, of which EGFR 19 del ( AF: 0.
16%), T790M (AF: 0.
20%), C797S (AF: 0.
38%).
In January 2019, the first-generation EGFR-TKI gefitinib combined with the third-generation osimertinib was selected for the patients, and the efficacy evaluation was performed one month later.
It was observed that the right lung lesions were reduced and the pleural effusion was reduced, and the side effects were minimal, and the efficacy was Evaluate as PR.
In September 2019, images showed disease progression.
Genetic testing showed EGFR 19del, T790M, and C797S cis mutations, including EGFR 19 del (AF: 0.
62%), T790M (AF: 0.
45%), and C797S (AF: 0.
57%) .
3Gefitinib treatment of PFS for 25 months.
C797S cis-mutation new program: Osimertinib combined with Anlotinib has a significant effect.
In September 2019, patients will be replaced with Osimertinib (80mg/QD) combined with Anlotinib (12mg/QD) and pemetrexed (800mg) + cisplatin (30mg 1-3day) regimens.
After 1 course of treatment, the images showed that the right lung lesions and pleural effusion were reduced, and the right lung infection was also relieved.
After two courses of combined treatment, cisplatin was discontinued due to serious gastrointestinal side effects.
A CT scan was performed again in December 2019, confirming that the patient is still in PR.
Subsequently, the patient received osimertinib + anlotinib maintenance treatment for up to five months until the disease progressed in May 2020.
In June 2020, the patient underwent NGS test again, and found EGFR 19del, T790M, C797S cis+trans co-mutation, including EGFR 19 del (AF: 0.
68%), T790M (AF: 0.
49%), C797S cis (AF) : 0.
24%) and C797S trans (AF: 0.
12%).
4 cis + trans C797S mutation: Bevacizumab combined with chemotherapy can help survival.
At this time, the patient's genetic test results showed that T790M C797S trans and cis appeared at the same time.
Previous studies have shown that chemotherapy plus bevacizumab can bring survival benefits after the emergence of cis-C797S mutation.
Therefore, starting from June 2020, the patient has been treated with bevacizumab combined with albumin paclitaxel.
After the treatment, the symptoms of chest discomfort and shortness of breath were relieved, and the patient's mental state and appetite were also improved.
The symptom relief was observed, but after two cycles, the treatment was stopped due to the patient's poor physical condition.
The patient passed away in August 2020, and the overall survival time was 39 months.
Treatment of the patient.
Case discussion This case proves that the transformation of T790M C797S trans mutation into cis mutation is a potential drug resistance mechanism that fails after the first-generation and second-generation EGFR-TKIs are used in combination.
At present, there are few treatment options for T790MC797S cis-mutant NSCLC.
Patients with such genomic characteristics in Europe and the United States mostly receive chemotherapy after osimertinib treatment progresses, but the clinical efficacy is poor.
Recently, preliminary clinical evidence has shown that chemotherapy combined with bevacizumab can achieve survival benefits after patients have both cis and trans mutations of C797S.
In this case, patients with triple mutations of EGFR 19del, T790M, and C797S cis mutations had a PFS of 9 months after treatment with anlotinib and osimertinib, and the maintenance treatment of osimertinib and anlotinib could be achieved.
Provide 5 months of PFS.
This case provides the first clinical evidence that the combination of osimertinib and anlotinib may be an effective therapy to overcome T790M C797S-mediated resistance.
This case also emphasizes the importance of dynamically monitoring the mutation status of osimertinib after treatment failure, which may provide patients with more opportunities for targeted therapy and improve the survival rate after osimertinib is resistant.
References: [1] Combination of Osimertinib and Anlotinib May Overcome the Resistance Mediated by in cis EGFR T790M-C797S in NSCLC: A Case Report
Osimertinib has been recommended by major authoritative guidelines and has become the standard treatment for second-line EGFR T790M mutation-positive NSCLC patients means.
At present, there is no standard for the treatment of non-small cell lung cancer (NSCLC) patients after osimertinib resistance in China.
Which treatment plan can bring greater survival benefits to patients? This article will use a real case to discuss the follow-up treatment of osimertinib resistance.
Case 1 The patient is female, 52 years old.
In June 2017, due to coughing for more than one month, I came to the hospital for treatment.
Chest CT showed that the right lower lung was consolidated, accompanied by right pleural effusion and miliary disseminated lung opacity.
PS score: 1.
Fiberoptic bronchoscopy + pathological examination revealed: stage IV (cTxNxM1) lung adenocarcinoma.
Genetic test: ARMS-PCR test found EGFR 19del.
1 T790M mutation appeared after gefitinib resistance.
In June 2017, because the patient's genetic test was EGFR 19del, gefitinib was selected as the first-line treatment for the patient.
In September 2017, imaging examination showed that the lesion reached partial remission (PR).
In January 2018, the image showed the disease progression, and the progression-free survival (PFS) was 7 months.
After the disease progressed in the first-line treatment of gefitinib, blood samples of the patient were tested and found a common mutation of EGFR 19 del (pE746_A750del, allele frequency (AF): 0.
07%) and T790M (AF: 0.
16%). In February 2018, the patient was switched to osimertinib for second-line treatment, and the efficacy evaluation reached PR.
In December 2018, chest CT scan showed enlarged right lung lesions, increased pleural effusion, and disease progression.
PFS was 10 Months.
2nd generation + 3rd generation EGFR-TKI: After osimertinib drug resistance, the second-line osimertinib treatment failed, NGS test was performed, and EGFR 19del, T790M, and T790M-C797S trans mutations were found, of which EGFR 19 del ( AF: 0.
16%), T790M (AF: 0.
20%), C797S (AF: 0.
38%).
In January 2019, the first-generation EGFR-TKI gefitinib combined with the third-generation osimertinib was selected for the patients, and the efficacy evaluation was performed one month later.
It was observed that the right lung lesions were reduced and the pleural effusion was reduced, and the side effects were minimal, and the efficacy was Evaluate as PR.
In September 2019, images showed disease progression.
Genetic testing showed EGFR 19del, T790M, and C797S cis mutations, including EGFR 19 del (AF: 0.
62%), T790M (AF: 0.
45%), and C797S (AF: 0.
57%) .
3Gefitinib treatment of PFS for 25 months.
C797S cis-mutation new program: Osimertinib combined with Anlotinib has a significant effect.
In September 2019, patients will be replaced with Osimertinib (80mg/QD) combined with Anlotinib (12mg/QD) and pemetrexed (800mg) + cisplatin (30mg 1-3day) regimens.
After 1 course of treatment, the images showed that the right lung lesions and pleural effusion were reduced, and the right lung infection was also relieved.
After two courses of combined treatment, cisplatin was discontinued due to serious gastrointestinal side effects.
A CT scan was performed again in December 2019, confirming that the patient is still in PR.
Subsequently, the patient received osimertinib + anlotinib maintenance treatment for up to five months until the disease progressed in May 2020.
In June 2020, the patient underwent NGS test again, and found EGFR 19del, T790M, C797S cis+trans co-mutation, including EGFR 19 del (AF: 0.
68%), T790M (AF: 0.
49%), C797S cis (AF) : 0.
24%) and C797S trans (AF: 0.
12%).
4 cis + trans C797S mutation: Bevacizumab combined with chemotherapy can help survival.
At this time, the patient's genetic test results showed that T790M C797S trans and cis appeared at the same time.
Previous studies have shown that chemotherapy plus bevacizumab can bring survival benefits after the emergence of cis-C797S mutation.
Therefore, starting from June 2020, the patient has been treated with bevacizumab combined with albumin paclitaxel.
After the treatment, the symptoms of chest discomfort and shortness of breath were relieved, and the patient's mental state and appetite were also improved.
The symptom relief was observed, but after two cycles, the treatment was stopped due to the patient's poor physical condition.
The patient passed away in August 2020, and the overall survival time was 39 months.
Treatment of the patient.
Case discussion This case proves that the transformation of T790M C797S trans mutation into cis mutation is a potential drug resistance mechanism that fails after the first-generation and second-generation EGFR-TKIs are used in combination.
At present, there are few treatment options for T790MC797S cis-mutant NSCLC.
Patients with such genomic characteristics in Europe and the United States mostly receive chemotherapy after osimertinib treatment progresses, but the clinical efficacy is poor.
Recently, preliminary clinical evidence has shown that chemotherapy combined with bevacizumab can achieve survival benefits after patients have both cis and trans mutations of C797S.
In this case, patients with triple mutations of EGFR 19del, T790M, and C797S cis mutations had a PFS of 9 months after treatment with anlotinib and osimertinib, and the maintenance treatment of osimertinib and anlotinib could be achieved.
Provide 5 months of PFS.
This case provides the first clinical evidence that the combination of osimertinib and anlotinib may be an effective therapy to overcome T790M C797S-mediated resistance.
This case also emphasizes the importance of dynamically monitoring the mutation status of osimertinib after treatment failure, which may provide patients with more opportunities for targeted therapy and improve the survival rate after osimertinib is resistant.
References: [1] Combination of Osimertinib and Anlotinib May Overcome the Resistance Mediated by in cis EGFR T790M-C797S in NSCLC: A Case Report
